Irritant oils from members of the genus Toxicodendron and Anacardiaceae, which include but are not limited to poison ivy, poison oak, poison sumac, and the Asiatic lacquer tree can cause a dermatological allergic reaction marked by erythema, vesiculation, and severe pruritus. These oils, like oils from other plants such as the capsicum genus and oils of non-plant origin produce limited eruptions of allergic dermatitis in response to the presence of these oils. The dermatitis often corresponds to areas where plants or the irritant oils have touched the skin or by contact with objects such as clothing, shoes, toys, tools, or pets acting as carriers of the irritant oils from previous exposure to the plants or oils. Further, serious lung irritation can be caused by the spreading of the irritant oils in smoke from the burning or these plants or oils.
An example reaction that results from the main constituent of the irritant oils from poison ivy and related plants occurs from urushiol. Urushiol is a mixture of several compounds which are derivatives of catechol with unsaturated C15 or C17 side chains as shown below.
wherein R can be one of the following:I=—(CH2)14CH3II=—(CH2)7CH═CH(CH2)5CH3III=—(CH2)7CH═CHCH2CH═CH(CH2)2CH3IV=—(CH2)7CH═CHCH2CH═CHCH═CHCH3V=—(CH2)7CH═CHCH2CH═CHCH2CH═CH3The exact composition of urushiol differs for each plant. For example, urushiol from poison ivy (T. radicans) is a mixture catechol derivatives wherein R is defined by I, II, III and V given above. Urushiol for the Asiatic lacquer tree (T. verniciferum) is a mixture catechol derivatives wherein R is defined by of I, II, III and IV given above.
Within 10-15 minutes after contact, urushiol binds to skin proteins. Washing off urushiol with soap and water before binding occurs can generally prevent an allergic reaction. However, once bound, urushiol cannot be washed off or transferred to other areas. Attached to cell membranes, urushiol is presented to patrolling T-cells, thus initiating an allergen-specific immune response. Generally, within 12 to 48 hours, redness and swelling appears, followed by blisters and itching. The rash occurs only where urushiol has touched the skin; however, the rash may appear to spread if it appears over time instead of all at once. This is usually because either the urushiol is absorbed in different parts of the body at different rates or exposure to urushiol-contaminated objects is repeated over time.
Less irritant oils related to urushiol include those related to the capsicum genus of plants that produce methyl hydroxyl derivatives of catechol with unsaturated C15 or C17 side chains in the para rather than ortho position. The capsicum oils produce sensations of heat as well as irritation. Capsaicin is the active ingredient that alters and enhances the sense of taste that leads to its common use as a spice for food. Most of the catechol derived spicy oils, while irritating, are less biological sensitizing and do not prevent their dietary use or consumption.
Contact dermatitis caused by exposure to urushiol is generally treated symptomatically. Itching is commonly treated with wet compresses, oral antihistamines, and topical hydrocortisones. Prescription topical corticosteroids are prescribed in severe cases when treatment is begun within a few hours of exposure. Prescription oral corticosteroids are given in severe cases where the rash appears on the face, genitals, or covers more than 30% of the body. When irritant oils are ingested, there is no current preparation that can be commonly used to alter the ensuing course of events, including sensations of heat discomfort nor gastrointestinal discomfort. Numerous over-the-counter products are used to dry up the blisters: aluminum acetate, baking soda, aluminum hydroxide gel, calamine, kaolin, zinc acetate, zinc carbonate, and zinc oxide.
Research for therapeutic agents to protect against or disrupt the allergic response to urushiol and irritant oils has involved numerous approaches including desensitization, vaccines, and barrier creams. In one study, postexposure treatment with a surfactant (DIAL® dishwashing liquid, oil-removing compound (GOOP® Hand Cleaner) or a chemical inactivator (Oak-N-Ivy Brand TECNU® Outdoor Skin Cleanser) reportedly provided 56-70% protection when compared to positive control (Stibich, et al. 2000. “Cost-effective post-exposure prevention of poison ivy dermatitis,” Int J Dermatol 39:515-518). Pre-exposure topical treatments and protectants have been reported: a topical lotion containing 5% quaternium-18 bentonite (Marks, et al. 1995. “Prevention of poison ivy and poison oak allergic contact dermatitis by quaternium-18 bentonite,” J Am Acad Dermatol 33:212-216); organoclay (Epstein, W. L. 1989. “Topical prevention of poison ivy/oak dermatitis,” Arch Dermatol 125:499-501); and topical skin protectant (TSP; ICD2289) (Vidmar, D. A. and Iwane, M. K. 1999. “Assessment of the ability of the topical skin protectant (TSP) to protect against contact dermatitis to urushiol (Rhus) antigen,” Am J Contact Dermat 10:190-197). Downregulation of contact sensitivity to urushiol in mice has been attempted by systemic treatment with various substances: a monoclonal antibody to urushiol (Baldwin, et al. 1999. “Regulation of the contact sensitivity response to urushiol with anti-urushiol monoclonal antibody ALG 991,” Arch Dermatol Res 291:652-658); and a synthetic I-Ak binding peptide coupled to 3-pentadecylcatechol (Gelber, et al. 1997. “Down-regulation of poison ivy/oak-induced contact sensitivity by treatment with a class II MHC binding peptide:hapten conjugate,” J Immunol 158:2425-2434). In one study, a 1:1 mixture of pentadecylcatechol and heptadecylcatechol diacetate was administered to human subjects in an effort to reduce sensitivity to poison ivy and poison oak, but reportedly decreased sensitivity was not achieved (Marks, et al. 1987. “Oral hyposensitization to poison ivy and poison oak,” Arch Dermatol 123:476-478).
U.S. Pat. No. 4,259,318 discloses use of the enzyme p-diphenol oxidase (laccase) as an effective topical treatment or prevention of poison ivy dermatitis.
U.S. Pat. No. 4,663,151 discloses use of aluminum chlorhydrate to prevent dermatitis caused by exposure to urushiol.
U.S. Pat. Nos. 4,803,047 and 4,594,239 disclose a method of neutralizing urushiol on surfaces with an aqueous solution comprising a water-soluble chlorine-containing compound.
U.S. Pat. No. 4,861,584 discloses a composition comprising an activated organophilic clay ion exchanged with a quaternary ammonium compound having aryl or alkyl groups in the range of 10-22 carbon atoms, and a vehicle comprising one or more long-chain hydrocarbons or volative silicon oils applied to the skin to block and absorb allergenic oils of toxic plants such as poison ivy.
U.S. Pat. No. 5,443,847 discloses a method for treating dermatitis caused by exposure to urushiol by topically applying a soluble manganese salt which acts as a chelating agent on urushiol, thus deactivating its toxicity.
U.S. Pat. No. 5,643,572 discloses compositions and methods of modulating immune responses to allergens such as urushiol using antibody molecules of either Ab1 or Ab2 reactivity to the sensitizing antigen.
U.S. Pat. Nos. 5,767,109 and 5,409,908 disclose use of cyclodextrins to complex urushiols to protect against and to treat irritation arising from exposure to urushiols.
U.S. Pat. No. 5,654,334 discloses N-L-aspartyl-L-phenyalanine 1-methyl ester (APM) and its derivatives as a pain reliever which is especially effective in relieving pain associated with osteoarthritis and multiple sclerosis. Further, International Application WO 97/00692 discloses APM as an antipyretic.
It has now been found that N-L-aspartyl-L-phenyalanine 1-methyl ester and its lower alkyl ester derivatives are effective in treating allergic dermatitis caused by exposure to plant-derived antigenic oils such as urushiol and that oral ingestion of N-L-aspartyl-L-phenylalanine 1-methyl ester also alters the duration, heat and irritation related to the intentional or accidental ingestion of spicy oils related to capsicum.